Pharmaceutical manufacturing processes produce medicinal compounds and products useful in treating a broad spectrum of health conditions and concerns. These processes often require large quantities of solvent or gas which result in the production of waste solvents, gases, and impurities. When possible, a waste stream is separated into its components, purified, and reused or recycled. Consequently, the separation and recovery of these manufacturing waste streams achieves cost savings in the industry as well as provides an ecological benefit to the environment.
Common pharmaceutical processes use silylation agents to react with active hydrogen present in molecules to form protector groups during the synthesis of compounds. Excess reagents and removed protecting groups are carried away in the solvent waste stream. When the reaction is carried out in solvents having a relative volatility near unity, i.e. the boiling point and volatility of the compounds are nearly the same, compounds become very difficult to separate and are often disposed off as waste.
Silylated compounds create complications in gas waste streams as well as solvent waste streams. During manufacturing processes, residual silylated compounds in a gas waste stream decompose to form silica which collects on equipment surfaces, creating a need for frequent maintenance and cleaning of the manufacturing equipment. Efficient in process methods of silica removal would reduce or eliminate downtime required for maintenance and cleaning of the manufacturing equipment.
Conventional methods of distillation have been unsuccessful at separating silylated compounds from solvent waste streams. Fractional distillation methods are generally known for separation of compounds having distinctly different boiling points and are not effective in separating components of an azeotropic composition. Other methods that have been described for separating silylated compounds require mixing a feed mixture with a separate reagent in a controlled reaction.
Recent methods of distilling a solvent mixture in the presence of a suitable reagent have been disclosed for separating solvent components having a relative volatility close to unity. These methods, known as reactive distillations, involve introducing an extractive agent into a distillation to affect the volatility of a feed component sufficiently to facilitate separation of the feed mixture.
U.S. Pat. No. 5,068,011 discloses an extractive distillation process for separating monoolefins from an alkane solvent with N-mercaptoalkyl-2-pyrrolidone.
Extractive distillation as described in U.S. Pat. No. 5,443,697 separates isomers of 1-heptene from heptane employing diacetone alcohol, ethylbutyrate and dimethylsulfoxide as the extractive agent.
Japanese Patent No. JP-112032 discloses a method of recovering 1,2-dichloroethane which is characterized by the fact that concentrated sulfuric acid is added to a mixed solution of 1,2-dichloroethane. The mixed solution is separated into two layers, rinsed, and dried over calcium chloride for dessication.
Consequently, there remains a need for convenient, effective methods of separation that provide for recovery of solvent and gas waste streams containing silylated compounds. One object of the invention is to provide a method of removing and optionally recovering silylated compounds from a solvent waste stream by a process of reactive distillation. Another object of the invention is to provide a method of recovering a purified solvent from the solvent waste stream. A further object of the invention is to provide a method of removing and optionally recovering silylated compounds from a gas waste stream. These and further objects of the invention will be apparent from the following description of the preferred embodiments thereof.